Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12-26 June 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 402 without deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on 12-14 March 2014 / signed on 12 May 2014)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Clear colorless liquid
- Storage Conditions: ca. 4 °C in the dark under nitrogen
Specific details on test material used for the study:
- Purity test date: 14 January 2014

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: At least 200 g
- Housing: Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. Animals were housed individually during the 24 h exposure period and in groups of five by sex for the remainder of the study.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 12 to 26 June 2014

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Pretreatment: On the day before treatment the back and flanks of each animal were clipped free of hair.
- Area of exposure: Back and flank area
- % coverage: Approximately 10 % of the total body surface area.
- Application of test item: Test item was used as supplied. The test item was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area) using a graduated syringe.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: After the 24 h contact period, the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test substance.
- Time after start of exposure: 24 h

TEST MATERIAL
- For the purpose of the study the test item was used as supplied. The specific gravity was determined (0.946) and used to calculate the appropriate dose volume for the required dose level.
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: Yes; 2.12 mL/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for mortality or clinical signs of toxicity at 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to Draize scale.
- Frequency of weighing: Individual bodyweights were recorded prior to application of the test substance on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes; at the end of the study animals were killed by cervical dislocation and subjected to gross necropsy.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
No mortality was observed.
Clinical signs:
- No signs of systemic toxicity were noted during the observation period.
- Very slight erythema was noted at the test site of three females. Small superficial scattered scabs and glossy skin were also noted at the test sites of two females with crust formation also noted at the test site of one female. There were no signs of dermal irritation noted at the test sites of all males and two females.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the dermal LD50 for ST 11 C 13 is higher than 2000 mg/kg bw in male/female rats therefore it is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of Wistar (RccHan™:WIST) rats (5/sex) was given a single dermal application of the undiluted test substance at 2000 mg/kg bw to intact skin of the back and flank area at the dose volume of 2.12 mL/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. 

 

No mortality or signs of systemic toxicity was observed. Very slight erythema was noted at the test site of three females. Other signs of dermal irritation noted were crust formation in one female and small superficial scattered scabs and glossy skin in two females. There were no signs of dermal irritation noted at the test sites of all males and two females. Animals showed expected gains in bodyweight over the 14 day study period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, the test substance is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS. 

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.